Indications

Antacids are a group of drugs that have been on the market for several years. They were initially first-line defense against peptic ulcer disease; however, the discovery of proton pump inhibitors revolutionized the treatment of peptic ulcer disease. Currently, antacid use is restricted for the relief of mild intermittent gastroesophageal reflux disease (GERD) associated heartburn.[1] The estimated prevalence of heartburn at least once per week in North America ranges from 18% to 28% with 25% adults reporting heartburn daily.[2][3][4][5]

Antacids are medications that do not require a prescription; in other words, they are self-prescribed. Antacids are a combination of various compounds with various salts of calcium, magnesium, and aluminum as the active ingredients. The antacids act by neutralizing the acid in the stomach and by inhibiting pepsin, which is a proteolytic enzyme. Each of these cationic salts has a characteristic pharmacological property that determines its clinical use. Antacids have therapeutic use for the following[6]:

Heartburn symptoms in GERD

Duodenal and gastric ulcers

Stress gastritis

Pancreatic insufficiency

Non-ulcer dyspepsia

Diarrhea caused bile-acid

Biliary reflux

Constipation

Osteoporosis

Urinary alkalinization

Phosphate binding in chronic renal failure

Mechanism of Action

The antacids reduce the acid reaching the duodenum by neutralizing the acid present in the stomach. The main objectives are:

Alleviating pain

Relieving pylorospasms

Avoid digestion and corrosion by acid chyme

The salts' mechanism of neutralization of acid varies, and each salt has a different mechanism with the ultimate goal of acid neutralization.

Aluminum Hydroxide

The formulation of aluminum hydrochloride and water results in neutralization of the acid in the stomach. It is also known to inhibit pepsin activity.[7] Aluminum hydroxide is complexed with a sulfated polysaccharide sucrose octasulfate to form sucralfate. This complex does not have a significant buffering action against the acid or has no effect on the pepsin secretion and does not alter the gastric acid production in any way.[8][9] Nevertheless, it is known to heal chronic ulcers and prevent acute mucosal damage induced chemically by reducing access to pepsin and acid. Sucralfate likes its aluminum hydroxide component is known to stimulate angiogenesis and granulation tissue formation.[8]

Aluminum hydroxide is also useful in hyperphosphatemia due to its ability to bind phosphate in the gastrointestinal (GI) tract and subsequently prevent absorption of phosphate.[10]

Calcium Salts

Calcium salts neutralize gastric acidity resulting in increased gastric and duodenal bulb pH; they additionally inhibit the proteolytic activity of pepsin if the pH is greater than 4 and increase lower esophageal sphincter tone. The calcium released from calcium carbonate is known to increase peristalsis in the esophagus, pushing the acid into the stomach and provide relief from symptoms of heartburn. The calcium salts also form combined insoluble compounds with dietary phosphate and prevent the absorption of later.[11]

The acid-neutralizing mechanism of the antacids is well understood, as mentioned above. In addition to this, other mechanisms add to the ulcer healing properties of this class of drugs. The exact mechanism is still unclear, but it is believed to be a combination of[12][7]:

Ability to promote angiogenesis

Bind to bile acids

Inhibit peptic activity

Suppress Helicobacter pylori growth

Administration

The dose for antacids depends upon the age of the patient, the purpose of administration (neutralization of acid or off-label use) and the presence of other comorbidities like renal or hepatic impairment. As all the forms of these medications are available as over the counter medication, the dosing recommendation varies by product/and or manufacturer.

Aluminum Hydroxide (Antacid)

Oral: Usually taken daily after meals and at bedtime at a dose of 640 mg up to 5 to 6 times a day with a maximum dose of 3840 mg per 24 hours.

Suspension The dose for suspension form is 320 mg/5 mL (473 mL). The suspension is to be shaken before use and is to be followed by water.

Hyperphosphatemia

Oral: Use is reserved for patients with serum phosphorus levels greater than 7 mg/dl.It is to be taken with meals at a dose of 300 to 600 mg three times a day, with use limited to a short period (4 weeks).[13]

Calcium Carbonate (Antacid)

It is used up to a maximum dose of 8000 mg per day up to 2 weeks with 1 to 4 tablets for symptomatic relief.

Antacids containing aluminum salts are safe to be used in pregnant women as well as for women during labor for aspiration prophylaxis. The information regarding the use of aluminum-containing antacids in breastfeeding females has not been studied, but aluminum is known to be endogenous to breast milk.[14][15] In the case of calcium-containing antacids, excessive use is to be avoided in pregnant women as calcium crosses the placenta. The amount of calcium reaching the fetus is dependent on the physiological changes in the mother. Maternal calcium intake also affects the amount of calcium excreted in breast milk; the currently prevailing opinion is that the use of calcium-containing antacids is safe during breastfeeding.[16]

Adverse Effects

The adverse effects are prominent in the infants and the elderly population. The chronic use of antacids in this population is not a recommendation due to safety concerns.

Aluminum Hydroxide:

Aluminum use is associated with an increased risk of toxicity in individuals with renal failure and infants. It presents as[17][18][19][20]:

Osteopenia

Microcytic anemia

Neurotoxicity

Osteomalacia

Constipation

Fecal impaction

Nausea

Vomiting

Abdominal cramps

Hypomagnesemia

Hypophosphatemia

Calcium Carbonate

The adverse reactions often seen with this group of antacids are[20][21]:

Abdominal pain

Anorexia

Constipation

Acid rebound

Nausea

Vomiting

Flatulence

Xerostomia

Headache

Xerostomia

Hypercalcemia

Hypophosphatemia

Milk-alkali syndrome

Contraindications

The absolute contraindication is hypersensitivity to any component of the formulation. Also, antacid agents require caution in patients with:

Renal failure

Heart failure

Edema

Cirrhosis

Low-sodium diets

Uremia

GI hemorrhages

Hyperparathyroidism

Renal calculus

Achlorhydria

Monitoring

The average therapeutic dose of antacid is 10 to 15 mL (1 tablespoon or 1 package content) of liquid or 1 to 2 tablets 3 to 4 times a day. Periodic monitoring of calcium and phosphorus levels is a suggested practice in patients on chronic therapy.

Toxicity

No information is available regarding toxicities caused by aluminum- and calcium-containing antacids. However, antacids are to be used cautiously in the high-risk population mentioned above.

Enhancing Healthcare Team Outcomes

Antacids are available as over the counter medications, meaning that patients do not require a prescription to obtain them. This situation results in the improper use of these medications with little to no relief of symptoms. There is a need to educate patients regarding the importance of a correct mode of administration, time of administration, and dosage for the prompt and prolonged relief of symptoms. These medications only provide symptomatic relief, which may mask an underlying disorder, but lack of awareness in this regard delays diagnosis in health conditions like GERD, peptic ulcer, gastric ulcer, and hiatal hernia. Although these medications do not cause toxicities in high doses, it is imperative to understand their interaction with other medicines, especially in patients on polypharmacy.

Nursing can verify drug use on intake and at each exam, and report to the treating physician. Pharmacists will encounter patients in the retail pharmacy and can counsel and educate patients on the advantages and pitfalls of antacid therapy, and inform the patient's treating physician if there any issues (drug-drug interactions, for example). Even a medication as apparently benign as OTC antacids can have significant effects on patient health, and the interprofessional team needs to work together and communicate to achieve positive outcomes. [Level V]

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A patient with complaints of heartburn goes to the pharmacy for an over the counter medication. He is relieved of the symptoms in a short span of time. What is the mechanism of action of the over the counter heartburn medication?

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A patient presents complaining of a burning sensation "behind her breastbone." This is the first time she has had this symptom. She denies any nausea, vomiting, chest pain, or shortness of breath. She does not want a prescription medication and would like to use an antacid. Which of the following would you recommend to her?

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A patient with untreated peptic ulcer disease experiences severe indigestion after a large meal. He opts to try an over-the-counter heartburn product and experiences uncontrolled bloating of the stomach and intense upper abdominal pain shortly after taking it. Endoscopic examination reveals that his ulcers are bleeding as a result of the gastric distension he experienced. Which over-the-counter heartburn product did he likely take?

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Shaker R,Castell DO,Schoenfeld PS,Spechler SJ, Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association. The American journal of gastroenterology. 2003 Jul [PubMed]

Eisen G, The epidemiology of gastroesophageal reflux disease: what we know and what we need to know. The American journal of gastroenterology. 2001 Aug [PubMed]

K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2003 Oct [PubMed]

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